1. Field of the Invention
The present invention relates to a system and method for use in biomedical research and nuclear medicine. More specifically, the present invention provides a radionuclide imaging method and apparatus to produce high-resolution images of the structure and function in small animals.
2. State of Technology
The demand for noninvasive methods to evaluate structure and function in small animals have driven researchers to adapt diagnostic imaging technologies commonly used for humans to make these technologies available for mice. Techniques to evaluate structure in small animals include magnetic resonance imaging, ultrasound, computed tomography (CT), as well as conventional x-ray imaging.
Background information on a micro CT apparatus (i.e., MicroCat) for imaging mice is described in, “A New X-ray Computed Tomography System for Laboratory Mouse Imaging,” by M. J. Paulus, H. Sari-Sarraf, S. S. Gleason, M. Bobrek, and D. K. Hicks, IEEE transactions On Nuclear Science, Vol. 46, No. 3, pp. 558-564, (1999), which provides the following description: “Two versions of a new high-resolution x-ray computed tomography system are being developed to screen mutagenized mice . . . . The first prototype employs a single-pixel cadmium zinc telluride detector with a pinhole collimator operating in a pulse counting mode. The second version employs a phosphor screen/CCD detector operating in a current mode. The major system hardware includes a low-energy x-ray tube, two linear translation stages and a rotation stage.”
Functional assessments of physiology and metabolism are typically performed with nuclear imaging of radiopharmaceuticals, including positron computed tomography (PET), variants of PET (e.g., MicroPET), and single-photon emission computed tomography (SPECT). Metabolic and functional in vivo imaging also can be performed using magnetic resonance spectroscopy and optical imaging of fluorescence or luminescent molecules.
Background information on PET is described in, “Development of a Small Animal PET Imaging Device with Resolution Approaching 1 mm,” by J. A. Correria, C. A. Burnham, D. Kaufman, and A. J. Fischman, IEEE transactions On Nuclear Science, Vol. 46, No. 3, pp. 631-635, (1999), which provides the following description: “The work presented here describes progress in the design and construction of a single-plane PET tomography having spatial resolution approaching 1 mm. The system consists of a 12 cm diameter ring with 360 LSO detectors viewed by 30 photo-multiplier tubes.”
Background information on MicroPET is described in, “A High Resolution PET Scanner for Imaging Small Animals,” by S. R. Cherry, Y. Shao, et al., IEEE transactions On Nuclear Science, Vol. 44, No. 3, pp. 1161-1166, (1997), which provides the following description: “It is also important to acknowledge that PET will never approach the fine resolution (˜100 μm) attainable with autoradiography. However, much useful information can still be obtained at 1-2 mm resolution, particularly in biodistribution studies, organ function studies and tumor studies, and PET has the significant advantage of preserving the animal intact for measurements at a later time.”
Background information on SPECT is described in, “ECG-Gated Pinhole SPECT in Mice with Millimeter Spatial Resolution,” by Max C. Wu, et al., IEEE transactions On Nuclear Science, Vol. 47, No. 3, pp. 1218-1221, (2000), which provides the following description: “Biomedical researchers have long used animal models to investigate mechanisms and treatment of human diseases. While earlier methods of generating appropriate models were primarily limited to identification of a genetic anomaly or surgical or pharmacological interventions, transgenic and knockout techniques have produced animals in which genetic alterations precisely define the disease phenotype. Because of their genetic similarity to humans, short reproductive cycle, and general ease of care, mice are most often used as transgenic models. Unfortunately, a mouse's small size (about 15-40 grams) often precludes traditional physiological measurement techniques, and typical heart rates of around 600 beats per minute complicate cardiovascular phenotyping.” The authors also state, “Radionuclide measurements of physiological functions in mice often are performed by tissue-counting or autoradiography, which requires sacrificing the animal.”
Background information on an ultra-high resolution SPECT system is described in, “Ultra-high resolution SPECT system using four pinhole collimators for small animal studies,” by K. Ishizu, et al., Journal of Nuclear Medicine, 36(12), pp. 2282-2286, (1995), which provides the following description: “The system utilizes a clinical four-head SPECT scanner with specially designed pinhole collimators . . . . The system provided a reconstructed spatial resolution of 1.65 mm (FWHM) and sensitivity of 4.3 kcps/micro Ci/ml with the best type of pinholes, respectively.”
Therefore, a need exists for high-resolution imaging techniques that allow anatomical or functional information to be obtained non-invasively, so that each animal can be studied repeatedly. By such techniques, each animal can serve as its own control in studies with a longitudinal design. Some animal models (particularly those involving pharmacologic or surgical intervention) can exhibit high variability from one animal to another. Therefore, significant benefits are achieved if the experimental design allows the evolution of disease or therapy to be followed in an individual animal. Other animal models involve a large investment in time and expertise (particularly transgenic animals and study of gene therapy protocols) and researchers need tools such as that taught in the present invention that can non-invasively assess biological function.
Accordingly, the present invention provides an apparatus and method for noninvasive functional imaging to allow studies in small animals, such as, mice, that will advance our understanding of biology, including human growth, development, and disease.